Several lines of previous investigation have suggested that alterations of ion transport by erythrocyte (RBC) membranes occur in some patients with affective disorders, and that such alterations may be related to diagnostic subtype or clinical state. We therefore propose to study lithium and sodium transport parameters in RBCs from depressed psychiatric patients and matched control subjects, and to combine these laboratory studies with concurrent clinical observations, in order to investigate the nature of possible membrane transport alterations in patients with affective illness. Specifically, we would attempt to determine: 1. whether characteristic alterations of RBC lithium transport parameters are found in patients with particular diagnostic subtypes of depression: 2. whether relationships exist between RBC membrane Na-K ions ATPase activity and clinical diagnostic subtype, severity of illness, or response to lithium treatment; and 3. whether functional alterations of net RBC sodium transport are manifested when RBCs from depressed patients are incubated under physiologic conditions in vitro. In order to address these questions, measurements of lithium influx and efflux rates, Na-K ions ATPase activity, and net ouabain-sensitive sodium efflux would be performed using RBCs obtained from drug-free bipolar and unipolar depressed patients, and from normal control subjects. Each patient would receive an extensive baseline clinical evaluation, including diagnostic interviews and measurements of symptom severity by means of clinical rating scales. Data from these studies would be used to address questions regarding possible relationships between membrane transport alterations and diagnostic subtype or initial severity of symptoms. The group of bipolar patients would subsequently be treated with lithium carbonate. Longitudinal measurements of clinical state, Na-K ions ATPase activity, and net ouabain-sensitive sodium efflux would be performed, so that an assessment could be made of membrane transport alterations and changes in clinical state occurring during such treatment. By these means, the proposed studies are intended to explore the nature of relationships between biological properties and clinical characteristics of depressed patients.